MR analysis and sensitivity analysis
We primarily employed the inverse variance-weighted (IVW) method to assess the impact of the telomere length on the percentage of different immune cells(15). Additionally, we utilized four supplementary analyses to confirm the results, including weighted mode, weighted median, simple mode, and MR-Egger regression(16-18). After conducting the MR analysis, we performed sensitivity analyses including heterogeneity and pleiotropy assessment. Heterogeneity among SNP-specific causal estimates was evaluated using meta-analysis methods. Therefore, Cochran’s Q statistic was calculated to measure heterogeneity between the estimated effects of individual telomere length associated SNPs on outcomes(19), the Pvalue greater than 0.05 indicating a lack of heterogeneity. To investigate whether the telomere length associated SNPs exhibit pleiotropy, the MR-Egger regression test was employed to identify potential pleiotropy, with a P value greater than 0.05 for the MR-Egger intercept indicating a lack of horizontal pleiotropy(18). Additionally, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) analysis was conducted to detect wide-ranging horizontal pleiotropy in the causal relationship(20). Furthermore, leave-one-out analysis was employed to identify relevant SNPs that may influence the causal effects and identify potential outliers. The relationship was quantified by calculating odds ratios (OR) with 95% confidence intervals (CI). Scatter plots and funnel plots were generated to provide a clear visualization.